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M Baumann

Publications and source records attributed to M Baumann.

At least 91 records · Page 5Linked to original sources
PubMed2000

[Which methods to minimize the time factor are substantiated by the evidence, which are unproven?].

BACKGROUND: Several experimental studies and randomized clinical trials demonstrate a decrease of local tumor control with increasing overall treatment time of fractionated radiotherapy. Proliferation of clonogenic tumor cells most likely is the major mechanism underlying this phenomenon. Important progress in radiation oncology might therefore be expected from inhibition of proliferation of clonogenic cells during radiation treatment. METHODS: Possibilities to minimize the time factor are briefly discussed. RESULTS AND CONCLUSIONS: Inhibition of proliferation of clonogenic tumor cells during irradiation by simultaneous chemotherapy, by inhibition of signal transduction pathways that stimulate proliferation, or by pharmacological inhibition of angiogenesis are scientifically interesting but currently not proven to be effective to counteract the loss of local tumor control with increasing overall treatment of fractionated irradiation. At present, the only established approach is to complete radiotherapy within a short overall treatment time, e.g. by accelerated fractionation and by prevention or compensation of unscheduled treatment gaps.

Angiogenesis Inhibitors↗
PubMed2000

[Livedo racemosa: an unusual late manifestation of borreliosis?].

Classic variants of cutaneous borreliosis are erythema chronicum migrans (ECM), lymphadenosis benigna cutis (LBC) and acrodermatitis chronica atrophicans (ACA). Other dermatoses have been reported in the literature as possibly linked to borreliosis. A 59-year old female patient was seen in the late phases of cutaneous borreliosis with histologically confirmed ACA. In addition, prominent livedo racemosa was seen on the legs, also showing tissue changes similar to those of ACA. Borrelia burgdorferi infection was serologically confirmed by the presence of anti-IgM and anti-IgG antibodies. The clinical spectrum of late cutaneous borreliosis should be enlarged to include livedo racemosa.

Acrodermatitis↗
PubMed2000

Formation of a phospholipid-linked pyrrolecarbaldehyde from model reactions of D-glucose and 3-deoxyglucosone with phosphatidyl ethanolamine.

Phospholipid-linked 'advanced glycation end products' (AGEs) are supposed to play an important role for lipid oxidation in vivo. The identification of the pyrrolecarbaldehyde 1-[2-formyl-5-(hydroxymethyl)-1 H-pyrrol-1-yl]-4,10-dioxo-7-(tetradecanoyloxy)-3,5,9-trioxa- 4lambda5-phosphatricosan-4-olate (7) from model reactions of D-glucose or 3-deoxyglucosone (4, 3-DG) with phosphatidyl ethanolamine (PE) is described. A preparation method is given for 1-(2-hydrox¿ethyl)-5-(hydroxymethyl)-1H-pyrrole-2-carbaldehyde (8). Independent syntheses as well as unequivocal structural characterization are reported for the substitution products of 8 1-(2-hydroxyethyl)-5-(methoxymethyl)-1H-pyrrole-2-carbaldehyde (9a) and 5-(ethoxymethyl)-1-(2-hydroxyethyl)-1H-pyrrole-2-carbaldehyde (9b). For all these compounds, chromatographic and spectroscopic data were established by GLC-MS and HPLC with diode array detection (DAD). PE and D-glucose or 3-DG 4 were either incubated at pH 7.4, 100 degrees C for 3 h or at pH 7.4, 37 degrees C for 5 weeks in neat buffer or ethanol buffer mixtures. The phospholipid fraction was purified on a C18 solid-phase extraction column and cleaved with ethanolic potassium hydroxide. The carbaldehyde 8, released in this process, was identified bs GLC-MS and quantified by HPLC-DAD. Formation of 7 is favored in the ethanol buffer reactions relative to those in buffer solution only although the amounts determined from the 37 degrees C incubations generally are very low. It seems likely, therefore, that phospholipid-linked pyrrolecarbaldehydes, such as 7, are biomarkers rather than effectors of membrane damage in vivo.

Aldehydes↗
PubMed2000

The PKC targeting protein RACK1 interacts with the Epstein-Barr virus activator protein BZLF1.

Phorbol esters reactivate Epstein-Barr virus (EBV) from latently infected cells via transcriptional activation of the viral immediate-early gene BZLF1. BZLF1 is a member of the extended AP-1 family of transcription factors that binds to specific BZLF1-binding motifs within early EBV promoters and to consensus AP-1 sites. Regulation of BZLF1's activity is achieved at the transcriptional level as well as through post-translational modifications. Recently, we reported that the transcriptional activity of BZLF1 is augmented by TPA [Baumann, M., Mischak, H., Dammeier, S., Kolch, W., Gires, O., Pich, D., Zeidler, R., Delecluse, H. J. & Hammerschmidt, W., (1998) J. Virol. 72, 8105-8114]. The increase of BZLF1's activity depends on a single serine residue (S186) that is phosphorylated by protein kinase C (PKC) in vitro and in vivo after stimulation with 12-O-tetradecanoylphorbol-13-acetate (TPA). Here, we identified RACK1 as a binding partner of BZLF1 in a yeast interaction trap assay. RACK stands for receptor of activated C-kinase and is involved in targeting activated PKCs and other signaling proteins. In vivo, RACK1 binds directly to the transactivation domain of BZLF1. Although a functional relationship between BZLF1 and PKC could be mediated by RACKs, RACK1 did not have a detectable effect on the phosphorylation status of BZLF1 in in vitro or in vivo phosphorylation assays. We suggest that RACK1 may act as a scaffolding protein on BZLF1 independently of activated PKCs.

Amino Acid Sequence↗
PubMed2000

Lack of effect of small high-dose volumes on the dose-response relationship for the development of fibrosis in distant parts of the ipsilateral lung in mini-pigs.

PURPOSE: Multi-field radiation therapy for intrathoracic tumours results in a heterogeneous dose distribution in lung tissue. This study investigated whether irradiation of small lung volumes with high fibrogenic doses affects the dose-response relationship for development of fibrosis in distant parts of the ipsilateral lung of mini-pigs. MATERIALS AND METHODS: The whole right lung of 26 'Mini-Lewe' pigs was irradiated with homogeneous doses of between 25 Gy and 40 Gy given in five equal fractions using opposing anterior-posterior portals and a linear accelerator. Another 32 animals were irradiated with a constant dose of 35 Gy to a small house-shaped high-dose field (base 3.0 cm, height 4 cm) located 3 cm caudolateral to the right hilus, while the surrounding right lung received either no irradiation or homogeneous doses of between 20 Gy and 30 Gy. The radiation fields were simulated and port films were obtained for each of the 10 fields in all pigs. Fibrosis was quantified 9 months after irradiation by determination of the hydroxyproline (HP) content of the 32 high-dose volumes and in the lung apex and the basolateral lung of all 58 pigs. Based on the reference value for the HP-ratio, i.e. the HP-concentration of the right lung over the left lung, obtained in 12 unirradiated control animals, the experimental results were converted into quantal data for probit analysis, a responder being an animal with an HP-ratio > 1.33. RESULTS: A dose-response relationship for the HP-ratio was obtained in the different lung sites and irradiation groups. For a given dose level the mean HP-ratios and response rates did not differ systematically between the lung apex and the basolateral lung. Probit analysis of the pooled data produced ED50 values of 21.8 Gy (95% CI 12-37) for irradiation without a high-dose volume and 25.9 Gy (24-28) for irradiation with a high-dose volume. These values are not significantly different. The results from both irradiation groups could be well fitted by a common dose-response curve with an ED50 value of 26.1 Gy. Unexpectedly, the response rates in the high-dose volume increased with increasing dose to the surrounding right lung. Analysis of the port films provided an explanation for this finding: inaccuracies in daily field positioning. When this error was corrected for by use of the mean dose to the high-dose volume, a dose-response curve with an ED50 of 25.2 Gy (22-29) was determined for the high-dose volume. CONCLUSIONS: The results of the study indicate that the irradiation of a small lung volume with high fibrogenic doses does not affect the dose-response relationship for development of fibrosis in distant parts of the ipsilateral lung.

Animals↗
PubMed2000

Effect of changing the weekly dose intensity of fractionated irradiation on local control of two human squamous cell carcinomas in nude mice.

PURPOSE: To compare the effect of fractionated irradiation with increasing, constant or decreasing weekly dose intensity on local tumour control. MATERIALS AND METHODS: Human squamous cell carcinomas, FaDu and GL, were grown in nude mice. Thirty fractions were applied under ambient conditions with increasing, constant or decreasing weekly dose intensity within a constant overall treatment time of 6 weeks. Dose intensity was changed every 2 weeks. Irradiations were terminated in some groups of animals after 20 fractions in 4 weeks. Endpoint was the tumour control dose 50% (TCD50) at day 120 (FaDu) or day 180 (GL) after end of treatment. RESULTS: In FaDu tumours the TCD50 value of 60 Gy (95% CI 56; 63) for fractionated irradiation with decreasing dose intensity, i.e. high initial doses, was slightly but significantly lower than the TCD50, of 68 (60; 81) after low initial doses (p=0.03). The TCD50 value of 62 Gy (57; 68) after constant doses was intermediate (constant vs increasing p =0.30; constant vs decreasing p=0.15). The higher efficacy of high initial doses in FaDu tumours was explained by local control occurring already during the course of irradiation. In GL tumours the TCD50 values were 52 Gy (43; 62) after high initial dose intensity, 50 Gy (43; 66) after constant doses, and 55 Gy (42; 89) after low initial dose intensity. These values were not statistically different (p-values 0.20-0.75). CONCLUSIONS: The data support the view that initial dose concentration during fractionated irradiation does not enhance radioresistance of FaDu and GL tumours, for instance by an earlier onset of clonogen repopulation.

Animals↗
PubMed2000

Automated surface and volume measurement of fused cells.

OBJECTIVE: To design and evaluate an algorithm to automatically calculate membrane area, volume and derived values from grey scale microscopic images of pairs of spheroid fused cells, especially human erythrocytes. STUDY DESIGN: Pairs of fused cells ("doublets") were identified by their high optical contrast, which resulted from their unhemolysed state. Global thresholding and noise-removing algorithms were applied to the image and resulted in a binary, "8"-shaped contour. The contour was used as a base for the calculation of a two-dimensional weighted distance histogram, the hilltops of which could be identified as center points of the contour's spheres. This allowed calculation of the distance of both center points and of the spheres' radii. With these three values, calculation of membrane area, volume and other derived values of the doublets became possible. High-speed time series were created based on consecutive images of the postfusion swelling and hemoglobin ejection from erythrocyte doublets at different temperatures. RESULTS: The influence of observation temperature on the dynamics of electrofused erythrocytes was measured with the algorithms given, and results were in agreement with physical changes in cell plasma viscosity. Images taken by optical and electron microscopy were in agreement with the two-spheres model of a doublet. The algorithm was not affected by fragmented contours. CONCLUSION: The velocity of hemoglobin ejection from electrofused erythrocytes and the relative change in static membrane area increase with temperature. The algorithm delivered reliable geometric values of fused cell configurations.

Algorithms↗
PubMed1999

Cellular transcription factors recruit viral replication proteins to activate the Epstein-Barr virus origin of lytic DNA replication, oriLyt.

DNA replication of Epstein-Barr virus (EBV) during the productive phase of the life cycle of this herpesvirus depends on the cis-acting element oriLyt. It consists of two essential domains, the upstream and the downstream component. Whereas the upstream component contains several DNA-binding motifs for the viral activator protein BZLF1, the downstream component is known to be the binding site of several cellular proteins. We identified cellular transcription factors that bind synergistically to a functionally relevant subsequence of the downstream component, the TD element. Two of these transcription factors, ZBP-89 and Sp1, stimulate replication as shown by protein fusions with the GAL4 DNA-binding domain and a single GAL4 DNA-binding motif inserted into the TD element. In protein binding assays, we observed an interaction of Sp1 and ZBP-89 with the viral DNA polymerase and its processivity factor. Our data indicate that cellular transcriptional activators tether viral replication proteins to the lytic origin via direct protein-protein interactions to assemble the viral replication complex at oriLyt.

Base Sequence↗
PubMed1999

Latent membrane protein 1 of Epstein-Barr virus interacts with JAK3 and activates STAT proteins.

Latent membrane protein 1 (LMP1) acts like a permanently activated receptor of the tumor necrosis factor (TNF)-receptor superfamily and is absolutely required for B cell immortalization by Epstein-Barr virus. Molecular and biochemical approaches demonstrated that LMP1 usurps cellular signaling pathways resulting in the induction of NF-kappaB and AP-1 via two C-terminal activating regions. We demonstrate here that a third region encompassing a proline rich sequence within the 33 bp repetitive stretch of LMP1's C-terminus is required for the activation of Janus kinase 3 (JAK3). The interaction of LMP1 and JAK3 leads to the enhanced tyrosine auto/transphosphorylation of JAK3 within minutes after crosslinking of a conditional NGF-R:LMP1 chimera and is a prerequisite for the activation of STAT transcription factors. These results reveal a novel activating region in the LMP1 C-terminus and identify the JAK/STAT pathway as a target of this viral integral membrane protein in B cells.

Amino Acid Sequence↗
PubMed1999

Palmitoyl-protein thioesterase, an enzyme implicated in neurodegeneration, is localized in neurons and is developmentally regulated in rat brain.

Palmitoyl-protein thioesterase (PPT) is an enzyme involved in cleavage of palmitate residues from acylated proteins. Mutations in PPT gene cause a severe neurodegenerative disorder, infantile neuronal ceroid-lipofuscinosis (INCL), characterized by loss of cortical neurons. In order to clarify the role of PPT and palmitoylation/depalmitoylation in the development of CNS and pathogenesis of infantile neuronal ceroid-lipofuscinosis (INCL), we studied the localization and expression of PPT in developing rats. Using immunohistochemical methods, we show for the first time that PPT is truly localized in neurons. Further, using RT-PCR and Western blotting, we show that expression of PPT in rat brain is developmentally regulated, with increasing expression during the maturation of CNS, reaching the maximum in young adulthood. The presented data support the view of PPT being essential for both development and maintenance of cortical neurons.

Animals↗
PubMed1999

The expression of palmitoyl-protein thioesterase is developmentally regulated in neural tissues but not in nonneural tissues.

Mutations in a palmitoyl-protein thioesterase (PPT) gene cause infantile neuronal ceroid lipofuscinosis (INCL). INCL is characterized by an extreme and selective neuronal loss in cerebral cortex and retina. Using reverse transcriptase PCR we show that PPT expression is developmentally regulated in rat brain and eyes but not in spleen. The changes in the expression coincide with developmental events in the brain. These data indicate that PPT has an important role in the development of the CNS.

Actins↗
PubMed1999

[Results of irradiation of inoperable stage III non-small cell lung cancer with 25Gy in five fractions].

BACKGROUND: Patients with advanced Stage III inoperable non-small cell lung cancer who were not suitable for irradiation with curative doses, were treated at the Department of Radiotherapy of the University Hospital of Dresden with 25 Gy in 5 fractions over 1 to 2 weeks. Survival of these patients was compared in this retrospective study to the survival of patients treated during the same period with 60 Gy in 30 fractions. PATIENTS AND METHOD: Between 1985 and 1994 298 patients were treated for a histologically or cytologically proven non-small cell lung carcinoma with 60 Gy in 30 fractions (n = 80), with 40 Gy in 20 fractions (n = 26) or with 25 Gy in 5 fractions (n = 192). Overall survival was determined using actuarial methods. Prognostic parameters were analyzed using uni- and multivariate tests. RESULTS: Median overall survival for all patients was 6 months (95% confidence interval 5; 7). In univariate analysis, survival of the patients treated with 60 Gy was significantly better than survival in the other groups. Median survival was 11 months (9; 13) after 60 Gy, 6 months (4; 8) after 40 Gy and 5 months (4; 6) after 25 Gy. In multivariate analysis the treatment schedule lost its significant influence on outcome of the therapy. The most important prognostic parameter was the performance status of the patients. CONCLUSIONS: When stratified for performance status as the most important prognostic parameter the survival time after hypofractionated irradiation to 25 Gy given in 5 fractions in 1 to 2 weeks was not significantly different from the results after conventional fractionation to 60 Gy. Hypofractionated radiation schedules are often more convenient for the patient, economical, and have been shown to be effective in symptom control. Thus, in clear palliative situations hypofractionated treatment with 25 Gy in 5 fractions or a comparable schedule appears to be a reasonable therapeutic option.

Actuarial Analysis↗
PubMed1999

[Delayed toxicity of brief preoperative irradiation and risk-adjusted postoperative radiotherapy of operative rectal carcinoma. Results of a randomized prospective study].

AIM: Analysis of a randomized study of preoperative radiation therapy for operable carcinoma of the rectum with regard to late sequelae. Results of tumor control and survival, which have already been published in detail are summarized for comparison and for confirmation of the conclusions. PATIENTS AND METHODS: Between January 1988 and October 1993 94 patients with operable carcinoma of the rectum were included in a randomized trial. Fourty-seven patients were treated with 5 x 3.3 Gy (field size 16 x 16 cm, 9 MeV photons) 24 to 48 hours prior to surgery; 46 patients did not receive preoperative irradiation. If risk factors (T4-stage, R1/R2 resection, intraoperative tumor perforation) were present, postoperative irradiation was performed after CT-planning. Total postoperative doses of 41.4 Gy (preoperative irradiation) or 59.8 Gy (surgery only) were applied with doses per fraction of 1.8 to 2.0 Gy. Local control, survival, and pattern of side effects were analyzed at 5 years after conclusion of the trial. RESULTS: The frequency of local recurrence was markedly reduced by preoperative irradiation of R0-resected patients (24% vs 13%, p = 0.08). The time to recurrence was delayed (1.9 vs 3 years). The 5-year actuarial survival rate was significantly higher in the preoperatively irradiated group compared to the not pre-irradiated group (40% vs 28%, p = 0.027). Multivariate analysis revealed UICC-grading as the only independent parameter for local control (p = 0.0003), while preoperative irradiation (p = 0.07) and T-stage (p = 0.08) only displayed a trend. For patient survival, age (p = 0.0003). R-status (p = 0.01) and UICC-score (p = 0.001) were significant prognostic factors. Preoperative irradiation had a non-significant effect only (p = 0.078). Radiation-induced side effects with a LENT-SOMA score > 2 were observed neither during frequent follow-up nor at an additional examination of those patients still alive in 1998 (n = 25). Of 4 pre- and postoperatively irradiated patients with risk factors, 3 had side effects grade 1 or 2, predominantly rectal changes, at 5 to 11 years after treatment. CONCLUSIONS: A positive effect on tumor control and survival is achieved with preoperative irradiation with the doses used in this study, with moderate side effects.

Actuarial Analysis↗